Functionally Distinct Dopamine Signals in Nucleus Accumbens Core and Shell in the Freely Moving Rat
Dynamic signaling of mesolimbic dopamine (DA) neurons has been implicated in reward learning, drug abuse, and motivation. However, this system is complex because firing patterns of these neurons are heterogeneous; subpopulations receive distinct synaptic inputs, and project to anatomically and funct...
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| Format: | Article |
| Language: | en_US |
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Society for Neuroscience
2016
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| Online Access: | http://hdl.handle.net/1721.1/104961 https://orcid.org/0000-0002-8269-2615 |
| _version_ | 1826217785392365568 |
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| author | Dreyer, Jakob K. Lovic, Vedran Aragona, Brandon J. Vander Weele, Caitlin Miya |
| author2 | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences |
| author_facet | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Dreyer, Jakob K. Lovic, Vedran Aragona, Brandon J. Vander Weele, Caitlin Miya |
| author_sort | Dreyer, Jakob K. |
| collection | MIT |
| description | Dynamic signaling of mesolimbic dopamine (DA) neurons has been implicated in reward learning, drug abuse, and motivation. However, this system is complex because firing patterns of these neurons are heterogeneous; subpopulations receive distinct synaptic inputs, and project to anatomically and functionally distinct downstream targets, including the nucleus accumbens (NAc) shell and core. The functional roles of these cell populations and their real-time signaling properties in freely moving animals are unknown. Resolving the real-time DA signal requires simultaneous knowledge of the synchronized activity of DA cell subpopulations and assessment of the down-stream functional effect of DA release. Because this is not yet possible solely by experimentation in vivo, we combine computational modeling and fast-scan cyclic voltammetry data to reconstruct the functionally relevant DA signal in DA neuron subpopulations projecting to the NAc core and shell in freely moving rats. The approach provides a novel perspective on real-time DA neuron firing and concurrent activation of presynaptic autoreceptors and postsynaptic targets. We first show that individual differences in DA release arise from differences in autoreceptor feedback. The model predicts that extracellular DA concentrations in NAc core result from constant baseline DA firing, whereas DA concentrations in NAc shell reflect highly dynamic firing patters, including synchronized burst firing and pauses. Our models also predict that this anatomical difference in DA signaling is exaggerated by intravenous infusion of cocaine. |
| first_indexed | 2024-09-23T17:09:07Z |
| format | Article |
| id | mit-1721.1/104961 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T17:09:07Z |
| publishDate | 2016 |
| publisher | Society for Neuroscience |
| record_format | dspace |
| spelling | mit-1721.1/1049612022-10-03T10:47:12Z Functionally Distinct Dopamine Signals in Nucleus Accumbens Core and Shell in the Freely Moving Rat Dreyer, Jakob K. Lovic, Vedran Aragona, Brandon J. Vander Weele, Caitlin Miya Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Vander Weele, Caitlin Miya Dynamic signaling of mesolimbic dopamine (DA) neurons has been implicated in reward learning, drug abuse, and motivation. However, this system is complex because firing patterns of these neurons are heterogeneous; subpopulations receive distinct synaptic inputs, and project to anatomically and functionally distinct downstream targets, including the nucleus accumbens (NAc) shell and core. The functional roles of these cell populations and their real-time signaling properties in freely moving animals are unknown. Resolving the real-time DA signal requires simultaneous knowledge of the synchronized activity of DA cell subpopulations and assessment of the down-stream functional effect of DA release. Because this is not yet possible solely by experimentation in vivo, we combine computational modeling and fast-scan cyclic voltammetry data to reconstruct the functionally relevant DA signal in DA neuron subpopulations projecting to the NAc core and shell in freely moving rats. The approach provides a novel perspective on real-time DA neuron firing and concurrent activation of presynaptic autoreceptors and postsynaptic targets. We first show that individual differences in DA release arise from differences in autoreceptor feedback. The model predicts that extracellular DA concentrations in NAc core result from constant baseline DA firing, whereas DA concentrations in NAc shell reflect highly dynamic firing patters, including synchronized burst firing and pauses. Our models also predict that this anatomical difference in DA signaling is exaggerated by intravenous infusion of cocaine. Lundbeck Foundation University of Copenhagen (2016 Excellence Programme for Interdisciplinary Research (DSIN)) National Institute on Drug Abuse (P01 DA031656) 2016-10-24T20:17:22Z 2016-10-24T20:17:22Z 2016-01 2015-11 Article http://purl.org/eprint/type/JournalArticle 0270-6474 1529-2401 http://hdl.handle.net/1721.1/104961 Dreyer, Jakob K., Caitlin M. Vander Weele, Vedran Lovic, and Brandon J. Aragona. “Functionally Distinct Dopamine Signals in Nucleus Accumbens Core and Shell in the Freely Moving Rat.” Journal of Neuroscience 36, no. 1 (January 6, 2016): 98–112. https://orcid.org/0000-0002-8269-2615 en_US http://dx.doi.org/10.1523/jneurosci.2326-15.2016 Journal of Neuroscience Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf Society for Neuroscience Society for Neuroscience |
| spellingShingle | Dreyer, Jakob K. Lovic, Vedran Aragona, Brandon J. Vander Weele, Caitlin Miya Functionally Distinct Dopamine Signals in Nucleus Accumbens Core and Shell in the Freely Moving Rat |
| title | Functionally Distinct Dopamine Signals in Nucleus Accumbens Core and Shell in the Freely Moving Rat |
| title_full | Functionally Distinct Dopamine Signals in Nucleus Accumbens Core and Shell in the Freely Moving Rat |
| title_fullStr | Functionally Distinct Dopamine Signals in Nucleus Accumbens Core and Shell in the Freely Moving Rat |
| title_full_unstemmed | Functionally Distinct Dopamine Signals in Nucleus Accumbens Core and Shell in the Freely Moving Rat |
| title_short | Functionally Distinct Dopamine Signals in Nucleus Accumbens Core and Shell in the Freely Moving Rat |
| title_sort | functionally distinct dopamine signals in nucleus accumbens core and shell in the freely moving rat |
| url | http://hdl.handle.net/1721.1/104961 https://orcid.org/0000-0002-8269-2615 |
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